A5034855510- Biochemical and Molecular Research
- Enzyme Structure and Function
- Tuberculosis Research and Epidemiology
- Amino Acid Enzymes and Metabolism
- Prion Diseases and Protein Misfolding
- RNA Research and Splicing
- Cancer Research and Treatments
- Cancer therapeutics and mechanisms
- Trace Elements in Health
- Microbial bioremediation and biosurfactants
- Enzyme Production and Characterization
- Mycobacterium research and diagnosis
- Bacteriophages and microbial interactions
- Metabolism and Genetic Disorders
- Polyamine Metabolism and Applications
- X-ray Diffraction in Crystallography
- Microbial metabolism and enzyme function
- Signaling Pathways in Disease
- Chemical Reactions and Isotopes
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Porphyrin Metabolism and Disorders
- Botulinum Toxin and Related Neurological Disorders
- Lipid Membrane Structure and Behavior
University of Alberta
2011-2025
Yale University
2007
Canadian Institutes of Health Research
2002-2003
Prion-like misfolding of superoxide dismutase 1 (SOD1) is associated with the disease ALS, but mechanism remains unclear, partly because difficult to observe directly. Here we study most misfolding-prone form SOD1, reduced un-metallated monomers, using optical tweezers measure unfolding and refolding single molecules. We find that folding more complex than suspected, resolving numerous previously undetected intermediate states consistent formation individual β-strands in native structure....
α-Synuclein is a protein that aggregates as amyloid fibrils in the brains of patients with Parkinson's disease and dementia Lewy bodies. Small oligomers α-synuclein are neurotoxic thought to be closely associated disease. Whereas fibrillization fibril morphologies have been studied extensively various methods, earliest stages aggregation properties oligomeric intermediates less well understood because few methods able detect characterize early-stage aggregates. We used fluorescence...
Significance Many diseases involve the propagation of misfolded proteins as in prion diseases. Compounds that can inhibit conversion into conformers exist, but their mechanism action remains poorly understood. By observing effects polymeric antiprion pharmacological chaperone pentosan polysulfate on folding single protein molecules, we find interactions with partially and fully unfolded states play an important role. A comparison to previous results for a very different chemical properties...
The synthesis of neoglycoconjugates has paved the way for discovery novel probes that mimic natural glycoconjugates and can provide designed research tools therapeutics. In some cases, target protein may not be amenable to harsh conditions, therefore semisynthetic or chemical methods must chosen with care. Here we present a simple modular chemoselective coupling strategy between an unprotected sugar N,O-disubstituted hydroxylamine under mild acidic conditions. This removes any need...
Mycothiol (1-d-myo-inosityl 2-(N-acetyl-l-cysteinyl)amido-2-deoxy-α-d-glucopyranoside, MSH or AcCys-GlcN-inositol (Ins)) is the major reducing agent in actinomycetes, including Mycobacterium tuberculosis. The biosynthesis of involves a deacetylase that removes acetyl group from precursor GlcNAc-Ins to yield GlcN-Ins. (MshB) corresponds Rv1170 M. tuberculosis with molecular mass 33,400 Da. MshB Zn2+ metalloprotein, and activity completely dependent on presence divalent metal cation. We have...
Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- horse-breeding industries. The arterivirus replicase gene encodes two large precursor polyproteins that processed by viral main proteinase nonstructural protein 4 (nsp4). three-dimensional structure 21-kDa nsp4 from prototype equine arteritis virus has been determined 2.0 Å resolution. Nsp4 adopts smallest known chymotrypsin-like fold with a canonical catalytic triad...
Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading neurotoxicity associated with Parkinson's disease and other neurodegenerative disorders. However, small difficult isolate for study. To gain better insight into the properties oligomers, we investigated engineered specific size (dimers, tetramers, octamers) linked head-to-tail in tandem, comparing behavior monomeric α-synuclein. All oligomeric constructs remained largely disordered solution, as determined...
Light scattering has been used for label-free cell detection. The angular light patterns from the cells are unique to them based on size, nucleus number of mitochondria, and surface roughness. collected can then be classified different image characteristics. We have also developed a machine learning (ML) method classify these patterns. As case study we this technique integrated with analyze staurosporine-treated SH-SY5Y neuroblastoma compare non-treated control cells. Experimental results...
The X-ray crystal structure of a conserved hypothetical protein molecular weight 16.3 kDa from Mycobacterium tuberculosis corresponding to open reading frame (ORF) Rv1155 has been solved by the multiwavelength anomalous dispersion method and refined at 1.8 Å resolution. revealed that is dimer in each monomer folds into large small domain; domain six-stranded antiparallel β-barrel flanked two α-helices helix–loop–helix motif. interface formed residues protruding primarily five six β-strands...
The crystal structure of a conserved hypothetical protein corresponding to open reading frame Rv2074 from Mycobacterium tuberculosis (Mtb) has been solved by the two-wavelength anomalous dispersion method. Refinement molecular at 1.6 Å resolution resulted in an Rwork 0.178 and Rfree 0.204. asymmetric unit contains monomer; however, crystallographic twofold symmetry operation space group P43212 generates dimeric Rv2074. Each monomer folds into six-stranded antiparallel β-barrel flanked two...